COVID-19 Miscellany

Tagged: COVID / MathInTheNews / PharmaAndBiotech / Politics / Statistics

Do you want the good news first?

The Good News

Be not afraid: it’s mostly good news. Mostly.

The FDA calendar

First up, the FDA calendar is full over the next 3 weeks. They’re meeting about boosters for the other vaccines, mix-n-match booster combinations, and the first kiddo vax:

That’s a lot, and we won’t be putting in the huge effort to live-blog all of them as we did previously for the Pfizer booster hearings. But we’ll try to hit the high points on the appropriate days.

I know people are really frustrated at the apparent glacial pace of all of this. But – trust me on this – they’re really moving at breakneck speed, while still ensuring everything is safe. The amount of compromise between all the gatekeepers needed is quite time-consuming. (You might argue we need fewer gate-keepers, but that would raise the risk of life-ending medical scams in normal times.) So this schedule looks really good to me!

Research on a pan-coronavirus vaccine

GenEngBiotechNews: NIAID grant for pan-coronavirus vax development NIAID: Notice of Special Interest in Pan-Coronavirus Vaccine Development Projects Second, from Genetic Engineering & Biotechnology News comes the report [1] that the National Institute of Allergy and Infectious Diseases (NIAID) has awarded $36 million for the development of a pan-coronavirus vaccine! The grat announcment itself [2] summarizes the purpose thus:

NIAID is issuing this Notice of Special Interest (NOSI) to highlight the critical need to develop prophylactic vaccines able to provide broad and durable protection against coronaviruses (CoVs), especially SARS-CoV-2 and others with pandemic potential. NIAID is particularly interested in highly collaborative, multi-disciplinary Program Projects (P01s) that incorporate understanding of CoV virology and immunology, immunogen design, and innovative vaccine and adjuvant platforms and technologies to discover, design, and develop pan-coronavirus (pan-CoV) vaccine candidates that provide broad protective immunity to multiple CoV strains.

UKRI: Types of Coronaviri Nat Rev Micro: origin & evolution of pathogenic coronaviruses Adv Vir Res: Hosts & sources of endemic human coronaviruses That’s not just against the SARS-CoV2 variant du jour, or even all its variants, but against all coronaviruses in general. Because there are about a bajillion of them. Ok, actually there are something like 7 that currently infect humans. [3] [4] [5]

Three are nasty: MERS, SARS, and SARS-CoV2. The other four cause mild respiratory diseases that, if you had them, you’d think you had a cold. But in nature… there are a bajillion kinds of coronaviruses infecting various animals. Given climate change, habitat destruction, and human bone-headedness, there will be more zoonotic transfers and probably more pandemics. Best nip that in the bud.

The notice was issued back in 2021-Nov, when we were all busy looking for any vaccine at all. It’s now been granted to the University of Wisconsin at Madison, Brigham & Women’s Hospital in Boston, and Duke University. Good luck to all of them.

So that’s both short-term and long-term good news. This whole panedemic has made me reflect on how lucky we’ve been to have just exactly the right technologies available: high-throughput sequencing, molecular level assays, mRNA synthesis techniques, lipid nanocapsules for delivery, and all the other stuff that came together at exactly the right moment.

Were it not for the fascists and the vaccine denialists intent on nihilism and burning, one might ascribe that to divine inspiration. Ok, maybe it is divine inspiration, and the bad parts are just us being us.

Mandates seem to work?

Third, everybody’s been saying mandates won’t work, people will quit jobs rather than get vaccinated, and so on. The media has been fueling this with their usual mathematically incompetent headlines. Here’s an example, with a correction helpfully supplied on Twitter:

Reuters wants to tell you all about the defiance of vaccines, telling irrelevant personal stories in loving detail. But the real story is that 99.4% of the employees at those hospitals decided to get vaccinated. Concentrating on the remaining 0.6% is just a waste of your time at best, and flagrantly deceptive at worst.

There are many similar results. For example, consider the Swiss Guard:

Mandates work. That’s the story.

Molnupiravir works

Herper at STAT: Molnupiravir reduces COVID-19 hospitalizations Fourth, from Matthew Herper at STAT News comes the usual good, solid stuff: this time a report on molnupiravir, an orally available COVID-19 therapy from Merck.[6] This drug candidate works by disrupting some of the genetic proofreading mechanisms in the virus, so that errors accumulate each time it divides and eventually is non-viable. In that respect, it’s like remdesivir; though unlike remdesivir it’s just a pill, not an infusion.

It has to be given early in the course of the disease, ideally before symptoms. That points to the need for a lot more testing of asymptomatic people, if this is going to do any good. Not to mention the logistics of pre-positioning the drug at every hospital in the world, so people who test positive can start on it immediately. And figure out how to pay the $700 each course of the drug will cost. (Have you considered that vaccines are both cheaper and already pre-positioned everywhere we can reach so far?)

The clinical trial showed 14.1% of the placebo patients were hospitalized or died, while 7.3% of the molnupiravir patients did so. While STAT News won’t calculate the efficacy from that, here at Chez Weekend we have no such inhibitions:

\[\begin{align*} \mbox{Efficacy} &= 100.0 \% \times \left(1 - \frac{p_\mbox{treatment}}{p_\mbox{placebo}}\right) \\ &= 100.0 \% \times \left(1 - \frac{0.073}{0.141}\right) \\ &= 48.2 \% \end{align*}\]

We can get a 95% confidence interval pretty easily here, too. That’s because the reporters at STAT News are not of the mathematically illiterate sort, and they give us enough information to calculate how many patients were in each arm:

  • 53 placebo cases were 14.1%, so there were 53/0.141 = 376 placebo subjects
  • 28 treatment cases were 7.3%, so there were 28/0.073 = 384 treatment subjects
> library("gsDesign") # For ciBinomial()
> mnpData <- matrix(c(53, 28, round(53/0.141), round(28/0.073)), nrow = 2, ncol = 2, byrow = FALSE,
                    dimnames = list(c("Placebo", "Treatment"), c("Ncases", "Ntotal"))); mnpData
          Ncases Ntotal
Placebo       53    376
Treatment     28    384

> ## Now calculate the efficacy, as above
> pPlacebo   <- mnpData["Placebo",   "Ncases"] / mnpData["Placebo",   "Ntotal"]
> pTreatment <- mnpData["Treatment", "Ncases"] / mnpData["Treatment", "Ntotal"]
> efficacy   <- round(100.0 * (1 - pTreatment / pPlacebo), digits = 2)

> ## Frequentist method: risk rates are scaled binomial, so we use the binomial
> ## confidence interval function in the gsDesign package.
> ci <- round(100.0 * (1 - rev(ciBinomial(mnpData["Treatment", "Ncases"],
                                          mnpData["Placebo",   "Ncases"],
                                          mnpData["Treatment", "Ntotal"],
                                          mnpData["Placebo",   "Ntotal"],
                                          scale = "RR"))),
              digits = 2)

> c(EfficacyLCL = ci[[1]], Efficacy = efficacy, EfficacyUCL = ci[[2]])
EfficacyLCL    Efficacy EfficacyUCL 
      20.45       48.27       66.47 
> 

Conclusions:

  • Molnupiravir has an estimated efficacy against hospitalization & death of 48.2%.
  • We’re 95% confident the true efficacy is between 20.45% – 66.47%.
  • Small study size ($N$ = 760) makes the 95% CI disappointingly wide.

We’re pretty sure it does something, i.e., it’s bounded away from 0. It’s likely that it reduces the risk of hospitalization & death by around half.

So… yeah, it’s nothing like the 90%+ efficacy of a vaccine that prevents you from getting sick in the first place, but it’s still good to reduce the risk of hospitalization and death by about half for those who do get sick.

And, of course, it’s not yet approved. That’s a whole ‘nother story, and more FDA hearings.

A Good Retraction: mRNA vax myocarditis risk is 1 in 25,000 — not 1 in 1,000!

Reuters fact check: retraction myocarditis study, real risk is 1 in 25,000 Fifth, there was a nasty preprint a few weeks back claiming that the incidence of myocarditis from the mRNA vaccine was a shockingly high 1 in 1000. This was instantly picked up on social media, and fueled the anti-vax firestorms in the usual venues. A lot of the conservative sites like Gateway Pundit particuarly hyped it (no, I will not link to the sewer).

Today from the fact checkers at Reuters comes a happy little notice that the study has been retracted. [7]

I won’t link to the retracted study because it looks like responsible people just made an honest mistake (Reuters does link, if you’re curious). But it was quite a blunder! They used the wrong denominator: there were 845,930 people vaccinated in their target population & period instead of just 32,379!

That lowers the rate of myocarditis by a factor of 25, taking the risk from an alarming 1 in 1000 to about 1 in 25,000. Something to be prepared for with mass vaccinations, but hardly the threat initially claimed.

The researchers were straightforwardly honest about the mistake, which speaks well of them and makes me want to treat them very gently and respectfully:

Our reported incidence appeared vastly inflated by an incorrectly small denominator (ie number of doses administered over the time period of the study). We reviewed the data available … and found that there had indeed been a major underestimation, with the actual number of administered doses being more than 800,000 (much higher than quoted in the paper).

This is why you should have a statistician check your work: figure out the correct base rate!

So… the risk of myocarditis is still low. The mRNA vaccines are still very, very safe.

…Aaaand the Rest

You just know when somebody says “first, the good news”… that some bad news is coming. Well, here we are.

The hospital situation grows worse

The Delta wave is causing problems everywhere, but especially in low-vaccination areas. Those hospitals are seeing a huge surge in unvaccinated patients, some making too-late requests for the vaccine, as they lay dying. These hospitals have had to institute what’s called “crisis standards of care”, i.e., forcing doctors to allocate resources to those most likely to live, and letting the rest die. This used to be called triage in the military, because you divide casualties into 3 groups: those who will die no matter what you do, those who can wait a bit, and those who will die unless you care for them now.

NYT: Triage in Alaska hospitals NYT: Surge in Alaska is worse than even the American South From the Times comes an article by Mike Baker, giving us stories of the trials of providing healthcare in Alaska. [8]

I’m slightly frustrated with this article, for the usual reasons: it concentrates on telling “human interest” stories of individuals, while not putting together the Big Picture that tells you what it all means. On the other hand, it’ does point to the heartbreaking consequences of our collective stupidity: people dying in hospital, and doctors being threatened by knuckleheads.

But when you look at the case rate in Alaska versus other regions of the US, it’s clear that right now it’s worse even than the American South! Testing supplies are exhausted, patients dying in hallways, doctors rationing oxygen! Sitting on the floor to suture up wounds, because there aren’t even enough stretchers! This is not the rational response of an advanced nation.

It’s important to appreciate the price of our stupidity in a public health crisis, and have that rubbed into our faces so we won’t do it again.

I don’t have much hope we’ll learn that.

What’s especially disappointing is the right-wing mobs who threaten violence against doctors who testified at the Alaska legislature’s hearings on masks. They of course screamed about using ivermectin, the de-worming med that’s an idée fixe delusion in their tribe. The doctors were told they had “sold out and are liars”, for reasons that are dramatically unclear. Another was arrested for disorderly conduct and carrying a concealed weapon. Some wore the Star of David, in an attempt to compare themselves to the victims of Nazi torture and genocide! Now, I’ve met holocaust survivors, and this is something a civilized person does not do.

And organized intimidation campaigns sometimes work: several doctors were afraid to go testify, and others required private security guards.

Think about that: doctors afraid for their safety from a mob, when there’s a pandemic on and those doctors are the only ones who can save lives. This is deeply stupid. Not to mention demonically vicious. I would almost propose demonic possession as a potential diagnosis of the American Republicans, if that were a thing that happened in the real world.

AP News: Surge in New England, despite high vax rates Now, you might think that I’m saying all this somewhat hautily from the fastness of Chateau Weekend, safely ensconced here in New England amongst the most highly vaccinated Americans. And you’d be partly right, I admit. But… there’s a wave here too, filling up our ICUs badly enough that AP News had to report it. [9]

Yes, we’re pretty highly vaccinated here: the low is 61.5% in New Hampshire, up to 69.4% in Vermont. I mean, hey: we’re not stupid, we want to live through this!

But even so, we have the same problems as everywhere else, just somewhat muted:

  • Vaccination isn’t uniform: our rural areas are less vaccinated like everywhere else, and that’s a feeding ground for Delta COVID and the breeding of even newer variants.
  • Also, given the ever-rising $R_0$ estimates for Delta, it now seems herd immunity is at about 90% immunity. If we can get to 70% vaccination and 20% “natural” immunity from survivors of infection, that might do it. But it would be better just to have everybody get vacinated: this won’t go away until we do, or else everybdoy who resists will be dead or infection-recovered.

Koch money funds and organizes borderline domestic terrorism

A lot of the vaccine resistance, mask resistance, and general resistance to rationality of any form seems repetitive. The people who show up are generally less educated. They tend to scream a lot. They threaten violence. They yell the same inanities about ivermectin, vaccine infertility, that Fauci somehow invented the SARS-CoV2 virus for some reason, that doctors are all lying, and so on.

Beziers Cathedral: built on site of a Cathar massacre Often their arguments are about religious freedom, but for religion of the worst sort: they effectively demand as much human sacrifice as a worshipper of Huitzilopochtli.

They remind me of this photograph I found just today, from Chris Bertram at Crooked Timber. The Cathédrale Saint-Nazaire-et-Saint-Celse de Béziers is indeed a beautiful building, and symbolic of much that is good in humanity. But it is founded on a vicious premise: in 1209, the Albigensian Crusade against the apparently harmless Cathars murdered over 20,000. The commander of the French forces, Simon de Montfort, 5th Earl of Leicester, seigneur de Monfort-l’Amaury, Viscount of Albi, Béziers and Carcassonne, and Comte de Toulouse, is supposed to have been not too picky about who was or was not a Cathar, when he ordered: “Caedite eos! Novit enim Dominus qui sunt eius.” (Kill them all! G-d will know his own.) Then the Béziers Cathedral was later built upon the ruins of the previous Cathar structure.

The best religion heals and cares for everyone, not just those who agree with us. The anti-vaxxers, the Albigensian crusaders, and the disciples of Huitzilopochtli are not practicing the best religion.

When the authoritarians get organized and use bad religion as a tool, they get dangerous.

WaPo: Koch money backs violent threats against school boards for mask mandates WaPo: Koch-funded protesters threatening Las Vegas school boards Rolling Stone: Koch dark money out to sink Biden And so it is today: from the WaPo comes news that the groups intimidating, for example, school boards, are in fact organized and funded by Koch family money. [10] Rolling Stone has an article with similar evidence [11] [12], possibly even more damning.

Apparently they particularly hate any effort to ameliorate climate change or to have a social safety net at all. Better to burn coal, and make people work cheaper because they’re afraid of dying, or so it seems from their actions. It’s a scandal that the Supreme Court decisions in recent years around dark money in politics allow this to be funded more or less in secret.

Here’s a thought: should it come to pass that you find yourself in a secret combination, taking money and talking points from the billionaires who best typify psychology’s dark triad, with demonic levels of narcissism, Machiavellianism and psychopathy… it’s time to re-think your life choices.

What’s the word we have for deliberate, organized intimidation and threats of violence for political purposes? Oh, that’s right: domestic terrorism.

The Weekend Conclusion

Times are bad. Mostly because we insist on making them bad, with self-inflicted wounds from the right wing. And self-inflicted wounds are the slowest to heal.

But times are also good: we have exactly the tools we need to fight the pandemic with amazing vaccines and increasingly good therapeutics; we’re trying to be equitable about it; and we’re looking to the future with pan-coronavirus vaccines to stop the next pandemic before it starts.

I prefer the latter. You should too. We have effective tools of science to be kind to one another, if only we could muster the will to do so.

Addendum 2021-Oct-05: The FBI Investigates

WaPo: Atty Genl Garland asks FBI to investigate From the WaPo comes news that Attorney General Merrick Garland has asked the FBI to investigate the groups threatening school boards in particular. [13] They protest mask mandates by ripping masks off people’s faces, they protest “critical race theory” (a complete hallucination) by threatening board members with “we know where you live”, they give Nazi salutes, they bring guns to school board meetings… the real suprise here is tht it took this much and this long to trigger FBI interest.

Of course, the reaction from the right is the usual Republican hysteria and accusations. Rep. Hawley, who apparently supported the Jan 6 seditious conspiracy to block the election counting, decided that the Biden administration was using the FBI to intimidate ordinary people. He’s clearly hallucinating; the problem of course is that he can get away with a Big Lie of this sort.

Allow me my little fantasy: what are the chances the FBI will nail the Kochs?


Notes & References

1: Author unnamed, “NIAID Awards $36 Million to Pan-Coronavirus Vaccine Development”, Genetic Engineering & Biotech News, 2021-Sep-29.

2: NIH Grants Notices, “Emergency Awards: Notice of Special Interest (NOSI) on Pan-Coronavirus Vaccine Development Program Projects, Notice Number: NOT-AI-21-002”, NIH Grants web site, 2020-Nov-10.

3: Author unnamed, “What is coronavirus? The different types of coronaviruses”, UK Research and Innovation, 2020-Mar-25 (updated 2020-Jul-07).

4: J Cui, F Li, ZL Shi, “Origin and evolution of pathogenic coronaviruses”, Nat Rev Microbiol 17:3, 181-192, 2019-Mar. DOI: 10.1038/s41579-018-0118-9.

5: VM Corman, D Muth, D Niemeyer, C Drosten, “Hosts and Sources of Endemic Human Coronaviruses”, Adv in Vir Res 100, 163-188, 2018-Feb-16. DOI: 10.1016/bs.aivir.2018.01.001.

6: M Herper, “Merck’s antiviral pill reduces hospitalization of Covid patients, a possible game-changer for treatment”, STAT News, 2021-Oct-01.

7: Reuters Fact Check, “Fact Check-Pre-print study that claimed 1 in 1,000 risk of myocarditis following COVID-19 vaccine was withdrawn due to miscalculation”, Reuters, 2021-Oct-01.

8: M Baker, “In Alaska’s Covid Crisis, Doctors Must Decide Who Lives and Who Dies”, New York Times, 2021-Oct-03.

9: W Ring, “Virus surge hits New England despite high vaccination rates”, AP News, 2021-Oct-03.

10: I Stanley-Becker, “Koch-backed group fuels opposition to school mask mandates, leaked letter shows”, Washington Post, 2021-Oct-01.

11: A Kroll & G Dembicki, “The Koch Empire Goes All Out to Sink Joe Biden’s Agenda — and His Presidency, Too”, Rolling Stone, 2021-Sep-30.

12: I never thought the day would come when I’d cite Rolling Stone as a reliable news source. But the failure of the mainstream media to get facts straight, and to rise above personal anecdote to the larger story is quite damning. And ever since Matt Taibbi’s 2010 RS article on the financial crash and Goldman Sachs, I’ve realized I have to take them (somewhat) seriously:

The world’s most powerful investment bank is a great vampire squid wrapped around the face of humanity, relentlessly jamming its blood funnel into anything that smells like money.

Indeed!

13: T Bella & D Barrett, “Garland asks FBI to address recent ‘disturbing spike’ in threats against educators”, Washington Post, 2021-Oct-05.

Written Mon 2021-Oct-04

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